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Flow Regulation by Opening the SepTum in Patients With Heart Failure; a Prospective, Randomized, Sham-controlled, Double-blind, Global Multicenter Study (FROST-HF)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05136820
Recruitment Status : Not yet recruiting
First Posted : November 29, 2021
Last Update Posted : November 29, 2021
Sponsor:
Information provided by (Responsible Party):
Occlutech International AB

Brief Summary:
The purpose of this clinical study is to assess the safety and effectiveness of the Atrial Flow Regulator in the treatment of subjects, 18 years of age or older, who have symptomatic heart failure with preserved ejection fraction (HFpEF) or heart failure with reduced ejection fraction (HFrEF) while on stable guideline directed medical therapy (GDMT) as outlined in the Guidelines for the Management of Heart Failure.

Condition or disease Intervention/treatment Phase
Heart Failure With Preserved Ejection Fraction (HFpEF) Heart Failure With Reduced Ejection Fraction (HFrEF) Device: Atrial Flow Regulator Device: Sham Comparator Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 575 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Patients will be identified from the investigator's pool of heart failure patients who are symptomatic on stable guideline directed medical therapy. An electronic randomization scheme in the EDC system will be used to minimize risk of bias in the investigation
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: The Interventional cardiologist will be unblinded and the Heart failure cardiologist and participants will be blinded. There will also be an unblinded study coordinator and a blinded study coordinator.
Primary Purpose: Treatment
Official Title: Flow Regulation by Opening the SepTum in Patients With Heart Failure; a Prospective, Randomized, Sham-controlled, Double-blind, Global Multicenter Study
Estimated Study Start Date : February 2022
Estimated Primary Completion Date : February 2026
Estimated Study Completion Date : February 2029

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure

Arm Intervention/treatment
Active Comparator: Randomization to 8mm AFR device
AFR Device 8mm vs Sham procedure
Device: Atrial Flow Regulator
Subjects will be randomized 1:1:1 where subjects will either receive the 8mm AFR device, 10mm AFR device or Sham procedure.
Other Name: AFR

Active Comparator: Randomization to 10mm AFR device
AFR device vs Sham procedure
Device: Atrial Flow Regulator
Subjects will be randomized 1:1:1 where subjects will either receive the 8mm AFR device, 10mm AFR device or Sham procedure.
Other Name: AFR

Sham Comparator: Randomization to sham procedure
Sham procedure to AFR device (8mm or 10mm)
Device: Sham Comparator
Subjects will be randomized 1:1:1 where subjects will either receive the 8mm AFR device, 10mm AFR device or Sham procedure.




Primary Outcome Measures :
  1. Primary Safety Endpoint for Major Adverse Cardiovascular and Neurologic Events (MACNE) within 12 months [ Time Frame: Baseline through 12 months ]
    Incidence of and time to MACNE within 12 months. MACNE includes all-cause mortality, stroke, systemic embolism, open cardiac surgery or major endovascular repair, and major bleeding (BARC 3-5).

  2. Composite Primary Efficacy Endpoint - Frequency of Cardiovascular Mortality [ Time Frame: Baseline through 12 - 24 months depending on rate of enrollment. The final primary endpoint analysis will occur when the last subject enrolled reaches their 12-month follow-up. ]
    Incidence of and time to cardiovascular mortality through 12-24 months

  3. Composite Primary Efficacy Endpoint - Frequency of heart transplant or Left Ventricular Assist Device (LVAD) [ Time Frame: Baseline through 12 - 24 months depending on rate of enrollment. The final primary endpoint analysis will occur when the last subject enrolled reaches their 12-month follow-up. ]
    Incidence of and time to heart transplant or LVAD

  4. Composite Primary Efficacy Endpoint - Total rate of Heart Failure Hospitalizations [ Time Frame: Baseline through 12 - 24 months depending on rate of enrollment. The final primary endpoint analysis will occur when the last subject enrolled reaches their 12-month follow-up. ]
    Total rate (first plus recurrent) per patient year of heart failure hospitalization admissions and time to first heart failure hospitalizations through 12-24 months

  5. Composite Primary Efficacy Endpoint - KCCQ Score [ Time Frame: Baseline through 6 months. The final primary endpoint analysis will occur when the last subject enrolled reaches their 12-month follow-up. ]
    Change in baseline KCCQ total summary score at 6-months


Secondary Outcome Measures :
  1. Clinical performance - change from baseline in NYHA Classification [ Time Frame: Baseline through end of study, approximately 5 years ]
    Clinical performance assessed by the change from baseline in NYHA Classification

  2. Clinical performance - change from baseline using KCCQ [ Time Frame: Baseline through end of study, approximately 5 years ]
    Clinical performance assessed by the change from baseline using KCCQ

  3. Clinical performance - change from baseline using EQ-5D [ Time Frame: Baseline through end of study, approximately 5 years ]
    Clinical performance assessed by the change from baseline using EQ-5D

  4. Clinical performance - change from baseline using the 6 Minute Walk Test (MWT) [ Time Frame: Baseline through end of study, approximately 5 years ]
    Clinical performance assessed by the change from baseline using the 6 Minute Walk Test (MWT)

  5. Components of the primary efficacy endpoint (cardiovascular mortality, heart failure hospitalization rate, heart transplant or LVAD placement). [ Time Frame: Baseline through 24 Months ]
    Analysis on components of the primary efficacy endpoint (cardiovascular mortality, heart failure hospitalization rate, heart transplant or LVAD placement).

  6. Components of Device Performance- Device placed in-situ as assessed by Investigator [ Time Frame: Implant through end of study, approximately 5 years ]
    Analysis on components of device performance (Device placed in-situ as assessed by Investigator)

  7. Components of Device Performance - Patency: Evidence of left to right shunt through AFR device [ Time Frame: Implant through end of study, approximately 5 years ]
    Analysis on components of device performance- Patency: Evidence of left to right shunt through AFR device as assessed by core lab

  8. Components of Device Performance- Implant embolization and clinically significant device migration [ Time Frame: Implant through end of study, approximately 5 years ]
    Analysis on components of device performance- Implant embolization and clinically significant device migration (i.e. SAEs probably related to device).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Written informed consent
  2. Aged ≥18 years
  3. Presence of chronic symptomatic HF (NYHA ≥class 2) and at least one of the following:

    1. Prior heart failure hospitalization within 6 months of informed consent, or
    2. Increased NT-proBNP
  4. If LVEF documented at screening is >55%, then must have one of either:

    1. Left atrial enlargement (LA diameter >2.3 cm/m2 or LA volume index >28 mL/m2), or
    2. PCWP ≥ 15mmHg at rest within previous 12 months, or
    3. LVEDP ≥15mmHg at rest within previous 12 months
  5. 6MWT
  6. Patients need to have maximally tolerated class 1 GDMT according to latest applicable guidelines (e.g., AHA or ESC), including CRT if appropriate, and a stable (no more than 100% increase or 50% decrease) dose diuretic.
  7. Using an acceptable method of contraception (for subjects of childbearing potential). Women of child-bearing potential will have a negative pregnancy test within 1 week of randomization.

Exclusion Criteria:

- General Exclusion Criteria

  1. Myocardial infarction and/or revascularization with percutaneous intervention (PCI) or coronary artery bypass grafting (CABG) within 3 months prior to informed consent
  2. Surgical or transcatheter valve (aortic, mitral, or tricuspid) repair or replacement within 2 months prior to informed consent
  3. Automated implantable cardioverter defibrillator (AICD) placement within 2 months prior to informed consent
  4. History of stroke, transient ischemic attack (TIA), deep vein thrombosis (DVT), or pulmonary emboli within 6 months prior to informed consent
  5. Advanced heart failure defined as current ACC/AHA Stage D heart failure
  6. Clinically significant valvular disease:

    1. mitral valve regurgitation grade ≥3+ MR, or
    2. tricuspid valve regurgitation grade ≥3+ TR, or
    3. aortic valve disease ≥3+ AR or ≥ moderate AS
  7. Uncontrolled hypertension, Systolic Blood Pressure (SBP) ≥160 or Diastolic Blood Pressure (DBP) ≥100 mmHg despite medical therapy at the time of screening visit
  8. Known clinically significant untreated carotid artery stenosis likely to require intervention, at discretion of investigator
  9. Current untreated coronary artery disease with indication for revascularization
  10. Any condition that limits exercise tolerance other than heart failure (e.g., peripheral vascular disease, orthopedic issues, angina, other)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05136820


Contacts
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Contact: Kelly Aspinwall 1-847-597-3201 kelly.aspinwall@occlutech.com

Sponsors and Collaborators
Occlutech International AB
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Responsible Party: Occlutech International AB
ClinicalTrials.gov Identifier: NCT05136820    
Other Study ID Numbers: G210281
First Posted: November 29, 2021    Key Record Dates
Last Update Posted: November 29, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
Keywords provided by Occlutech International AB:
Heart Failure
Preserved Ejection Fraction
Reduced Ejection Fraction
HFpEF
HFrEF
Additional relevant MeSH terms:
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Heart Failure
Heart Diseases
Cardiovascular Diseases